Ischemia causes oxygen deprivation, cell injury and related organ dysfunctions, such as heart failure, stroke, chronic obstructive pulmonary disease, ischemic retinopathy, liver injury and acute renal failure. Mitochondrial dysfunction is a key factor in organ ischemia injury; upon loss of oxygen, mitochondrial oxidative phosphorylation rapidly stops, with a resulting loss of the major source of ATP production for energy metabolism.
Erythropoietin (EPO) is essential for the regulation of the mass of erythrocytes in response to changes in tissue oxygenation during hypoxia and anemia. The protective effects of EPO have been demonstrated in various tissues and experimental models of ischemia-induced injury and have been attributed to its effect on non-haematopoietic metabolic adaptation, inhibition of apoptosis and stimulation of angiogenesis. Recently, EPO has been reported to stimulate cardiac mitochondrial proliferation through the activation of mitochondrial biogenesis, which is mediated by PPAR co-activator 1-α (PGC-1α), a key regulator of cardiac bioenergetics. Clinically, EPO reverses cardiac remodeling, improves cardiac function, and enhances the exercise tolerance and quality of life of patients by inducing protective effects beyond the correction of anaemia (Bergmann et al., 2011). These findings highlight the possibility that EPO-mediated protection may depend on its modulatory effects on intracellular energetic.
Haemoglobin (Hb) is the main oxygen transporter in erythrocytes. Its main form, Hb-α, is a tetramer consisting of two α- and β-polypeptide chains, each carrying a haeme group. Recently, Hb was unexpectedly found to be expressed in many non-haematopoietic cells and it is possible that it facilitates tissue oxygen transport or increases cellular oxygenation and so provides an intrinsic protective mechanism against hypoxic/ischemic injury.
Recombination Human Erythropoietin (rHuEPO) is used for treating chronic heart failure, it can reverse cardiac remodeling, improve heart function, antiapoptotic effects, anti-inflammation, anti-fibrosis and also improving aneamia symptom and sport capacity. However, high dosages of rHuEPO were needed for the treatment, and it caused higher rates of thrombosis and stroke. Darbepoetin alfa was proved to increase the risk of stroke in anemic, heart failure patient and chronic kidney disease patient and not even have a significant treatment efficacy. Moreover, according to the result of REVEAL trail, epoetin alfa did not reduce infarct size and was associated with higher rates of adverse cardiovascular events and increase in infarct size among older patients.
In conclusion, clinical practice should avoid rHuEPO treatment to higher hemoglobin targets, particularly in those with significant cardiovascular morbidity and those who require disproportionately high dosages of rHuEPO to achieve recommended hemoglobin levels. Compare to rHuEPO, small molecular compound can easily go through myocardial tissue to the myocardial cells. Therefore, it is necessary to develop a drug which is a small molecular compound, low-dosage needed and stimulating endogenous EPO.
Astragalus propinquus (syn. Astragalus membranaceus) is the dried roots of Astragalus membranaceus (Fisch.) Bge. Var. Mongholicus (Bge.) Hsiao or Astragalus membranaceus (Fisch.) Bge., which are the plants of the family Fabaceae. It is the most widely used herbs in traditional Chinese medicine because it can help diuretic, lower blood pressure and enhance energy.
In previously study, Astragalus propinquus is known that rich in polysaccharides, glucuronides, several amino acids, cholines, flavonoids and folates, etc. However, the extractions from Astragalus propinquus by present technology are the mixture. Therefore, it is necessary to develop a novel preparation method to obtain a pure and small molecule component of Astragalus propinquus. 